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. 2018 Mar 6;16(1):49.
doi: 10.1186/s12967-018-1420-z.

Safety, tolerability and efficacy of intra-articular Progenza in knee osteoarthritis: a randomized double-blind placebo-controlled single ascending dose study

D Kuah  1 , S Sivell  2 , T Longworth  3 , K James  4 , A Guermazi  5 , F Cicuttini  6 , Y Wang  6 , S Craig  2 , G Comin  7 , D Robinson  8 , J Wilson  2
Affiliations

Safety, tolerability and efficacy of intra-articular Progenza in knee osteoarthritis: a randomized double-blind placebo-controlled single ascending dose study

D Kuah et al. J Transl Med. .

Abstract

Background: Cell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG.

Methods: We conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40-65 years with symptomatic Kellgren-Lawrence grade 1-3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months.

Results: The study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events [143/169 (84.6%)] were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p ≤ 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm3, 95% CI 13.56 mm3, 199.37 mm3, p = 0.028).

Conclusion: When administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG's potential for disease modification in OA. Trial registration ANZCTR, ACTRN12615000439549. Date registered: 7th May 2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368355.

Keywords: Allogeneic stem cells; Intra-articular injection; Knee function; Knee osteoarthritis; Knee pain; Magnetic resonance imaging; Mesenchymal stem cells; Visual analogue scale; WOMAC.

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Figures

Fig. 1
Fig. 1
Study CONSORT flow diagram
Fig. 2
Fig. 2
a Change from baseline VAS pain scores (data are presented as the least squares mean estimates with 95% confidence intervals and within group p values) and b proportion of pain responders (responders with an improvmeent of at least 30% from baseline VAS score). VAS, visual analogue scale
Fig. 3
Fig. 3
Change from baseline in WOMAC a pain subscale scores, b stiffness subscale scores and c physical function subscale scores. Data are presented as the least squares mean estimates with 95% confidence intervals and within group p values. WOMAC Western Ontario McMaster Universities Arthritis Index
See this image and copyright information in PMC

References

    1. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1323–1330. doi: 10.1136/annrheumdis-2013-204763. - DOI - PubMed
    1. AIHW. Osteoarthritis Canberra: Australian Institute of Health and Welfare; 2016 (18 September 2017).
    1. Hunter DJ, Riordan EA. The impact of arthritis on pain and quality of life: an Australian survey. Int J Rheum Dis. 2014;17(2):149–155. doi: 10.1111/1756-185X.12232. - DOI - PubMed
    1. Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. 2013;386(9995):743–800. doi: 10.1016/S0140-6736(15)60692-4. - DOI - PMC - PubMed
    1. Buttgereit F, Burmester GR, Bijlsma JW. Non-surgical management of knee osteoarthritis: where are we now and where do we need to go? RMD Open. 2015;1(1):e000027. doi: 10.1136/rmdopen-2014-000027. - DOI - PMC - PubMed

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